Abstract

Background

For patients with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in patients with cystic fibrosis.

Objectives

To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in patients with cystic fibrosis.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov trials registry to obtain information on unpublished and ongoing studies.

Date of latest search: 22 August 2013.

Selection criteria

Randomised and quasi-randomised studies.

Data collection and analysis

We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias.

Main results

While two studies met our inclusion criteria, we did not include them in the review because the investigators of the studies did not report any information specific to patients with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future updates of the review.

Authors' conclusions

The lack of currently available evidence makes it impossible to make conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among patients with cystic fibrosis after lung transplantation. A recent Cochrane review comparing tacrolimus with cyclosporine in all patients with lung transplantation (not restricted to patients with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among patients with cystic fibrosis after lung transplantation.

Plain language summary

Drugs to suppress the immune system after lung transplantation in patients with cystic fibrosis

Lung transplantation is an available and realistic treatment option for patients with cystic fibrosis whose lungs are severely damaged. However, as a natural defence mechanism, the body recognises a transplanted lung as foreign and activates the immune system to reject it. This is known as graft rejection. To prevent this, drugs are needed to suppress the immune system after lung transplantation. There are several different types of such drugs that act by suppressing different components of the immune system. Much of the research on such drugs has focused on all patients after lung transplantation, and not specifically on patients with cystic fibrosis. Currently, clinicians do not all agree on a common way of using such drugs in patients with cystic fibrosis after lung transplantation.

We searched for randomised studies of drugs to prevent graft rejection in patients with cystic fibrosis after lung transplantation so we could assess the effects of each drug on its own or combined with other drugs compared to 'dummy' treatment (placebo) or other single drugs or combinations of drugs. Although we found two eligible studies, they included patients with a number of chronic conditions and not just cystic fibrosis. The results were given for all patients and we were unable to extract results that were specific to patients with cystic fibrosis. We contacted the researchers who conducted these randomised studies, but they have not yet sent us the results that were specific to patients with cystic fibrosis. We will include these results in future updates of this systematic review, if we receive them.

A review of drugs to suppress the immune systems of lung transplant patients in general (not restricted to those with cystic fibrosis) only included three studies which had a high risk of bias. The review did not find that any one drug was better than another for reducing the chances of death or acute rejection; but tacrolimus led to a lower risk of long-term rejection and high blood pressure, although there was a higher risk of diabetes. Research is needed on the use of drugs that suppress the immune system in patients with cystic fibrosis who have received a lung transplantation.